Research Article

Synthesis and Evaluation of ¹⁹⁸Au/PAMAM-MPEG-FA against Cancer Cells

Author(s):

Reza Rezaei, Simin Janitabar Darzi* and Mahnaz Yazdani   Pages 1250 - 1265 ( 16 )

Abstract:

Background: There is a significant dearth of clinical biochemistry researches to evaluate the facility of exploitation of folate targeted radioactive gold-labeled anti-cancer drugs against various cancer cell lines.

Objective: The aim of this paper was to develop a gold-based compound with an efficient therapeutic potential against breast cancer. To this end, the synthesis of the ¹⁹⁸Au/PAMAM-MPEG-FA composite was considered here.

Methods: The radioactive gold (¹⁹⁸Au) nanoparticles were encapsulated into Folic acid (FA)-targeted Polyamidoamine dendrimer (PAMAM) modified with Maleimide-Polyethylene glycol Succinimidyl Carboxymethyl ester (MPEG). After that, anticancer assessments of the prepared ¹⁹⁸Au/PAMAM-MPEG-FA hybrid mater against breast cancer were investigated.

Further studies were also devised to compare the anticancer capabilities of the ¹⁹⁸Au/PAMAM-MPEG-FA composite with the synthesized P-MPEG, ¹⁹⁷Au/P-MPEG, ¹⁹⁷Au/P-MPEG-FA, ¹⁹⁷Au/P-FA and ¹⁹⁸Au/P-MPEG-FA conjugates. The prepared drugs were characterized by means of various analytical techniques. The radionuclidic purity of the ¹⁹⁸Au/P-MPEG-FA solution was determined using High Purity Germanium (HPGe) spectroscopy and its stability in the presence of human serum was studied. The cell uptake and toxicity of the prepared drugs were evaluated in vitro, and some comparative studies of the toxicity of the drugs were conducted towards the MCF7 (Human breast cancer cell), 4T1 (Mice breast adenocarcinoma cell) and C2C12 (Mice muscle normal cell).

Results: The results showed that cell uptake of ¹⁹⁸Au/P-MPEG-FA nanoparticles is high in the 4T1 cell line and the order of uptake is as 4T1> MCF7> C2C12. Moreover, of the tested compounds, ¹⁹⁸Au/P-MPEG-FA had the highest toxicity towards the cancerous 4T1 and MCF7 in all concentrations after 24, 48 and 72h (P < 0.001). Furthermore, the cytotoxicity of the drugs was concentration-dependent.

Conclusion: On the basis of the present research, ¹⁹⁸Au/P-MPEG-FA has been proposed as a good candidate for the induction of cell death in breast cancer, although further experimental and clinical investigations are required.

Keywords:

Radioactive gold, PAMAM dendrimer, drug targeting, cellular uptake, toxicity, folate.

Affiliation:

Department of Biochemistry, Faculty of Science, Zanjan University, 45371-38791, Zanjan, Nuclear Science & Technology Research Institute, Materials and Nuclear Fuel Research School, Tehran, 14395-836, R&D Department, Toronto Institute of Pharmaceutical Technology, Toronto, Ontario, M1P 4X4

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